Subdural Hematoma in Non-accidental Head Injury

Subdural hematoma in infants and young children happens most frequently, but not exclusively, in the setting of non-accidental head injury. Irrespective of the etiology, this injury type can be associated with a variety of pathophysiologic changes, including those which appear to affect the relationship between substrate delivery and metabolic demand. The exact underpinnings and necessary conditions for these changes remain incompletely understood but appear to be specific for children during early development. This chapter will review the clinical presentation, spectrum of mechanisms, and neuroanatomic and cerebrovascular considerations for this common and often serious injury type

Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact

The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma

Assessing Nursing and Pediatric Resident Understanding of Delirium in the Pediatric Intensive Care Unit

Delirium is a common disease process in the pediatric critical care unit, yet practices for screening and prevention vary drastically between institutions. The authors hypothesized that surveying pediatric residents and nurses who care for patients in the intensive care setting would expose misunderstandings about delirium. They brought to light common incorrect beliefs that benzodiazepines are appropriate therapy for delirium and that children who are delirious will not have memories of the experience. Many nurses and residents listed that they were not comfortable or were extremely uncomfortable identifying delirious patients. Findings demonstrate an opportunity to improve on nursing and resident knowledge

Biomarkers in Moderate to Severe Pediatric Traumatic Brain Injury: A Review of the Literature

Despite decades of research, outcomes in pediatric traumatic brain injury (pTBI) remain highly variable. Brain biofluid-specific biomarkers from pTBI patients may allow us to diagnose and prognosticate earlier and with a greater degree of accuracy than conventional methods. This manuscript reviews the evidence surrounding current brain-specific biomarkers in pTBI and assesses the temporal relationship between the natural history of the traumatic brain injury (TBI) and measured biomarker levels. A literature search was conducted in the Ovid, PubMed, MEDLINE, and Cochrane databases seeking relevant publications. The study selection and screening process were documented in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Extraction forms included developmental stages of patients, type and biofluid source of biomarkers, brain injury type, and other relevant data. The search strategy identified 443 articles, of which 150 examining the biomarkers of our interest were included. The references retrieved were examined thoroughly and discussed at length with a pediatric neurocritical care intensivist specializing in pTBI and a Ph.D. scientist with a high degree of involvement in TBI biomarker research, authoring a vast amount of literature in this field. TBI biomarkers might serve as valuable tools in the diagnosis and prognosis of pTBI. However, while each biomarker has its advantages, they are not without limitations, and therefore, further research is critical in pTBI biomarkers

Inflammasomes as biomarkers and therapeutic targets in traumatic brain injury and related-neurodegenerative diseases: A comprehensive overview

Given the ambiguity surrounding traumatic brain injury (TBI) pathophysiology and the lack of any Food and Drug Administration (FDA)-approved neurotherapeutic drugs, there is an increasing need to better understand the mechanisms of TBI. Recently, the roles of inflammasomes have been highlighted as both potential therapeutic targets and diagnostic markers in different neurodegenerative disorders. Indeed, inflammasome activation plays a pivotal function in the central nervous system (CNS) response to many neurological conditions, as well as to several neurodegenerative disorders, specifically, TBI. This comprehensive review summarizes and critically discusses the mechanisms that govern the activation and assembly of inflammasome complexes and the major methods used to study inflammasome activation in TBI and its implication for other neurodegenerative disorders. Also, we will review how inflammasome activation is critical in CNS homeostasis and pathogenesis, and how it can impact chronic TBI sequalae and increase the risk of developing neurodegenerative diseases. Additionally, we discuss the recent updates on inflammasome-related biomarkers and the potential to utilize inflammasomes as putative therapeutic targets that hold the potential to better diagnose and treat subjects with TBI.This work is partially supported by the grant "UL1TR002736, Miami Clinical, and Translational Science Institute, from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities" (PI: J C. Munoz Pareja). Additionally, this work was also supported by grants from NIH for (PI: Yehia Mechref) (1R01GM112490-09, 1U01CA225753-05, and 1R01GM130091-04) and for (PI: JPdRV) (1R01NS113969-01, 1RF1NS125578-01)

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasome-dependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasome-dependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline

Blood-based traumatic brain injury biomarkers - Clinical utilities and regulatory pathways in the United States, Europe and Canada

Traumatic brain injury (TBI) is a major global health issue, resulting in debilitating consequences to families, communities, and health-care systems. Prior research has found that biomarkers aid in the pathophysiological characterization and diagnosis of TBI. Significantly, the FDA has recently cleared both a bench-top assay and a rapid point-of-care assays of tandem biomarker (UCH-L1/GFAP)-based blood test to aid in the diagnosis mTBI patients. With the global necessity of TBI biomarkers research, several major consortium multicenter observational studies with biosample collection and biomarker analysis have been created in the USA, Europe, and Canada. As each geographical region regulates its data and findings, the International Initiative for Traumatic Brain Injury Research (InTBIR) was formed to facilitate data integration and dissemination across these consortia. This paper covers heavily investigated TBI biomarkers and emerging non-protein markers. Finally, we analyze the regulatory pathways for converting promising TBI biomarkers into approved diagnostic tests in the United States, European Union, and Canada. TBI biomarker research has significantly advanced in the last decade. The recent approval of an iSTAT point of care test to detect mild TBI has paved the way for future biomarker clearance and appropriate clinical use across the globe

Sustainable cleft care through education : the first simulation-based comprehensive workshop in the Middle East and North Africa region

Objective: To describe the conduct of the first multidisciplinary simulation-based workshop in the Middle East/North Africa region and evaluate participant satisfaction. Design: Cross-sectional survey-based evaluation. Setting: Educational comprehensive multidisciplinary simulation-based cleft care workshop. Participants: Total of 93 workshop participants from over 20 countries. Interventions: Three-day educational comprehensive multidisciplinary simulation-based cleft care workshop. Main Outcome Measures: Number of workshop participants, number of participants stratified by specialty, satisfaction with workshop, number of workshop staff, and number of workshop staff stratified by specialty. Results: The workshop included 93 participants from over 20 countries. The response rate was 47.3%, and participants reported high satisfaction with all aspects of the workshop. All participants reported they would recommend it to colleagues (100.0%) and participate again (100.0%). No significant difference was detected based on participant specialty or years of experience. The majority were unaware of other cleft practitioners in their countries (68.2%). Conclusion: Multidisciplinary simulation-based cleft care workshops are well received by cleft practitioners in developing countries, serve as a platform for intellectual exchange, and are only possible through strong collaborations. Advocates of international cleft surgery education should translate these successes from the regional to the global arena in order to contribute to sustainable cleft care through education

Sustainable Cleft Care Through Education: The First Simulation-Based Comprehensive Workshop in the Middle East and North Africa Region

Objective: To describe the conduct of the first multidisciplinary simulation-based workshop in the Middle East/North Africa region and evaluate participant satisfaction. Design: Cross-sectional survey-based evaluation. Setting: Educational comprehensive multidisciplinary simulation-based cleft care workshop. Participants: Total of 93 workshop participants from over 20 countries. Interventions: Three-day educational comprehensive multidisciplinary simulation-based cleft care workshop. Main Outcome Measures: Number of workshop participants, number of participants stratified by specialty, satisfaction with workshop, number of workshop staff, and number of workshop staff stratified by specialty. Results: The workshop included 93 participants from over 20 countries. The response rate was 47.3%, and participants reported high satisfaction with all aspects of the workshop. All participants reported they would recommend it to colleagues (100.0%) and participate again (100.0%). No significant difference was detected based on participant specialty or years of experience. The majority were unaware of other cleft practitioners in their countries (68.2%). Conclusion: Multidisciplinary simulation-based cleft care workshops are well received by cleft practitioners in developing countries, serve as a platform for intellectual exchange, and are only possible through strong collaborations. Advocates of international cleft surgery education should translate these successes from the regional to the global arena in order to contribute to sustainable cleft care through education